Parkinson's disease is a chronic, progressive, hypokinetic disorder characterized by impaired voluntary movement (See, Dale and Federman (eds.), WebMD Scientific American Medicine, NY: WebMD Corporation, Chapter 11, Section 15, pp. 1-21, 2001; Lang and Lozano, N Engl J Med, 339:1044, 1998; and Lang and Lozano, N Engl J Med, 339:1130, 1998). Parkinson's disease occurs as a result of the death of dopamine-producing neurons in the substantia nigra of the midbrain. Dopamine is a neurotransmitter, or chemical messenger, that transports signals to the parts of the brain that control movement initiation and coordination. The loss of dopamine in the brain is associated with multiple primary symptoms including: tremor of the hands, arms, legs, jaw, and face; rigidity or stiffness of the limbs and trunk; bradykinesia or slowness of movement; and postural instability or impaired balance and coordination.
Parkinson's disease afflicts more than one million persons in the United States alone (Lang and Lozano, supra, 1998), with approximately 50,000 new cases diagnosed each year. It is generally a disease of late middle age, with typical onset occurring at about age 60. About five percent of patients, however, have early-onset disease and are younger than 40 when symptoms begin.
Most current treatment strategies for Parkinson's disease (PD) focus on symptom control through one or more of medication, surgery, and physical therapy. The dopamine precursor, levodopa (L-DOPA) is still considered to be the gold standard in terms of treatment for PD (Schapira and Olanow, JAMA, 291:358-364, 2004). Unfortunately, L-DOPA can cause debilitating side effects (LeWitt and Nyholm Neurology, 62:S9-S16, 2004), including severe nausea, vomiting, and psychosis. Moreover, with prolonged use, patients frequently experience other side effects such as dyskinesias (spontaneous, involuntary movements) and “on-off” periods when the medication will suddenly start or stop working.
Surgical treatments are considered for patients with advanced disease or who have not responded adequately to medications. Accepted surgical treatments involve either the creation of small, precise lesions or the implantation of stimulating electrodes in specific brain regions that appear to be overactive in Parkinson's disease. More recently, implantation of fetal dopaminergic tissue has been utilized as a means of restoring dopamine levels in the brains of patients with Parkinson's disease (See, e.g., Freed et al., Arch Neurol, 47:505-512, 1990; and Lindvall et al., Science, 247:574-577, 1990). These types of methods, however, are highly invasive.
Thus, what is needed in the art are noninvasive treatment strategies for effectively controlling symptoms of Parkinson's disease and other movement disorders. In addition, it would be desirable to be in possession of therapy regimens that maximize the efficacy of existing medicines.